Compounding: FAQ for Veterinarians

Are You Playing by the Rules?

Q: What is compounding?A: Simply put, compounding is any manipulation of a drug beyond that stipulated on the drug label. Veterinary drugs should only be compounded based on a licensed veterinarian's prescription, and to meet the medical needs of a specific patient.

Some states allow veterinarians to prescribe compounds for administration to patients in the practice; but depending on state rules, it is typically not legal to dispense medications previously compounded by a pharmacy to leave the veterinary practice with clients, so state rules should be reviewed and followed.

Examples of compounding include: mixing two injectable drugs in the same syringe;

creating an oral suspension from crushed tablets or an injectable solution;

adding flavoring to a commercially available drug;

creating a transdermal gel for a drug typically taken through other routes;

mixing two solutions for instilling into the ear.

View a compounding brochurethat was developed by the Animal Health Institute, the American Veterinary Distributors Association, and the AVMA.

Q: How is compounding regulated?A: It's regulated by both the federal government (Food and Drug Administration/FDA) and state governments. At the federal level, the FDA regulates compounding for animal patients as a subpart of its Extralabel Drug Use (ELDU) Rules. FDA also has a Compliance Policy Guide (CPG)which describes more about how it regulates compounding for animals and what activities it defers to the state. The FDA says it generally defers day-to-day regulation of compounding by veterinarians and pharmacists to state authorities. The state boards of pharmacy oversee pharmacy practices within the states, while the state veterinary medical boards oversee the practice of veterinary medicine, including prescribing. Before using a pharmacy, veterinarians should also consider whether the pharmacy is compliant with the United States Pharmacopeial Convention (USP)standards, such as General Chapters <795> and <797> for non-sterile and sterile compounding for both humans and animals.

Q: Are pharmacists trained to compound for animals?A: Many pharmacy schools do not include any veterinary pharmacotherapy in their curricula so most veterinary-specific pharmacy training (including compounding) is obtained through independent continuing education on the part of the pharmacist. Since drugs and compounds may behave differently in animals than in humans, veterinarians should ask compounding pharmacists if they have specialized training or credentials in veterinary compounding, and veterinarians should specifically seek the compounding services of pharmacists who have specialized knowledge of veterinary compounding.

Q: How do compounded medications differ from the ones I or my clients can get from a store or regular pharmacy?A: Federal rules require that the compounded medications on by modified versions of what you would otherwise buy at the store or pharmacy. In other words, FDA says they should be FDA-approved drugs that have been crushed, have had a flavor added, or otherwise tweaked, and that they should not be brand new medications (i.e. assembled from non-FDA approved ingredients), or FDA asserts they are technically "new animal drugs" which are required to have FDA approval in order to be legally sold.

Q: Are compounded drugs the same as generic drugs?A: No, they are not the same as generic drugs. A generic drug is a non-brand-name version of a drug: for example, Tylenol® is the brand name for this drug used in human medicine, but acetaminophen is the generic name. In general, buying a generic drug with the same ingredient and same strength as the brand name is equivalent to (but often cheaper than) buying the brand name version. Veterinary extralabel use of human generic drugs in animals is allowed under specific conditions delineated within federal law.

Generic drugs are approved by the FDA. They have to be shown to be safe and effective; their label has to be approved by FDA; their manufacturing facilities have to follow certain FDA specifications; and the manufacturer is required to continually ensure the shelf stability of the product. FDA assigns an equivalency rating to human generic drugs which states whether the generics are therapeutically equivalent (achieve the same therapeutic goal) as compared to the branded product. Generic animal drugs have an Abbreviated New Animal Drug Application (ANADA) number assigned by the FDA, which you can typically find on the container. Compounds and unapproved drugs lack an ANADA number.

When a drug is compounded, the new form of that drug no longer performs in the same manner as the approved drug. Yes, the compound still incorporates the same drug ingredient, but the composition of the dosage form has been changed and you can't expect it to be identical in every way to the original drug. Compounding may cause changes in stability, bioavailability, metabolism and elimination of the drug.

Q: When is compounding necessary? A: Compounding for non-food animals may be necessary when approved drugs need to be modified to sufficiently treat the patient (e.g. flavoring, diluting, or changing the form of medications from tablet to suspension).For example, if you need to prescribe methimazole (Felimazole®) for a hyperthyroid cat but the owner tells you the cat will not allow the owner to “pill” it, you might need to have the product compounded into a liquid form so the cat can be adequately treated.

Compounding for non-food animals might also be necessary when no approved drug exists, or if the approved drug isn’t commercially available to treat a pet’s diagnosed condition. There are two general sets of circumstances in which the AVMA believes compounding from bulk ingredients (i.e., “raw” active ingredients) may be necessary:

the approved drug is not commercially available, or

the needed compounded preparation cannot be made from the approved drug.

Q: When is compounding legal? What criteria must be met?A: Compounding is considered legal when federal and state rules are followed. Veterinarians can inquire about state licensure from the relevant state boards of pharmacy prior to prescribing compounds. Federal extralabel drug use regulations specifically permit compounding from FDA-approved drugs when a veterinarian believes there is a need to alter the approved drug to adequately medicate a non-food animal with a diagnosed medical condition. This means that there an established Veterinarian-Client-Patient Relationship (VCPR); the individual patient has a medical condition for which a prescribed medication is needed; and the veterinarian determines that a compounded drug is needed for the animal. To be in line with FDA’s Extralabel Drug Use Rules, compounding should be performed using the FDA-approved drug.

For example, let’s say you need to prescribe a particular FDA-approved antimicrobial for an ear infection in a dog, but the antimicrobial only comes in an injectable form. Following the FDA’s rules, you could mix the antimicrobial – for example, amikacin – with normal saline for instilling into the ear.

Q: When is compounding illegal or unethical?A: According to the FDA’s Compliance Policy Guide (CPG), examples of situations where FDA might use enforcement action include:

Using commercial-scale equipment to compound in large quantities (compounding should be done on an individual patient basis)

Compounding large quantities not intended for use in a specific patient, and then re-selling it to veterinarians or animal owners

For example: there is an FDA-approved product in paste form for treating stomach ulcers in horses. Any compounding pharmacy that compounds what they call "generic Gastrogard" in a paste form is making an illegal product because they are duplicating an already-approved product. The product, Gastrogard®, contains omeprazole (also found in human products such as Prilosec®) and has been proven effective in clinical studies. In reality, compounded omeprazole paste is not a generic form of the drug – it is a copy of an FDA-approved product, which is illegal. In addition, in one study, compounded omeprazole was found to be not effective compared with the approved form of the drug. For a write-up about the study, view the article on TheHorse.com. Recall that veterinarians must comply with all aspects of the federal extralabel drug use regulations including record-keeping and labeling requirements.

Q: Are there different compounding rules/regulations applied to use in food-producing animals?A: Yes, and those rules are much more stringent. Using a compounded drug in food animals is only reserved for when there is absolutely no other choice for treating that animal’s medical condition and when safe use of that animal for human food purposes can be predicted following discontinuation of the drug. See AVMA’s Extralabel Drug Use Algorithmfor more information. Also refer to the FDA’sCompliance Policy Guide. All federal requirements for use of drugs in food producing animals still apply, including that the veterinarian must establish a substantially extended withdrawal interval for the compounded preparation supported by appropriate scientific information, and the compound must be prescribed within the veterinarian-client-patient-relationship.

Q: What is a "mimic" drug?A: A mimic is a compounded drug that is produced to copy an FDA-approved human or animal drug, but avoids the drug approval process and is usually compounded for economic reasons and not medically necessary therapeutic reasons. It is clearly outside the bounds of traditional compounding and it is illegal to produce mimic drugs. In addition, although these mimic drugs may appear identical to the FDA-approved product, there may be differences that affect the product's efficacy or safety. The production and prescribing of compounded mimic drugs is illegal.

Use of a mimic drug is bad for several reasons:

It denies the patient treatment with an approved drug proven to be safe, effective, pure, potent, stable and made under FDA-mandated "good manufacturing practices."

It exposes the patient to substances that have not been proven safe and effective and could be contaminated, sub- or super-potent, or unstable.

It exposes parties involved in mimicry to unnecessary liability.

It undermines the incentive for research and development oriented animal pharmaceutical companies to market new animal drugs. Without a healthy animal pharmaceutical industry veterinarians will have fewer approved therapies.

Q: Is it acceptable to prescribe a compounded medication that is the same as an available brand-name or generic medication because it's cheaper in the compounded form? A: Cost is not an appropriate reason for compounding from bulk ingredients. If you use a compounded drug only because it's cheaper, you could be putting your patient's health at risk by using a drug that hasn't been proven safe and effective. There are times when compounding may be necessary, but it isn’t necessary when there’s an FDA-approved drug that can adequately treat your patient’s condition.

Q: How can I find a reputable compounding pharmacy?A: Check your state board of pharmacy for information on which pharmacies are licensed to do business within your state. In addition, there are independent, third-party bodies (for example – the Pharmacy Compounding Accreditation Board) that accredit pharmacies meeting certain criteria.

Q: What is the AVMA's stance on compounding? A: We have two policies on compounding:

Q: Can vaccines be compounded?A: Unlike FDA’s rules, there is no term called “compounding” when it comes to USDA’s rules (USDA is the federal regulatory authority governing animal vaccines).

When you’re reconstituting a vaccine to administer to a patient, be sure you are doing so according to the manufacturer’s directions. Mixing multiple vaccines in one syringe for administration is illegal, could be a liability issue, and could render the vaccines useless or even harmful especially if they are adjuvanted vaccines.

Q: How can I know that the compounded medication prescribed and dispensed for my patient is safe and effective? A: You don’t have the assurances with a compounded drug that you would have with an FDA-approved drug that the drug will effectively and safely treat your patient. Ways you can help to ensure therapeutic success in this scenario is to 1) determine if a compounded drug is really necessary; 2) prescribe from a reputable and trustworthy compounding pharmacy, 3) ask the pharmacist to provide evidence to support the stability and assigned expiration date (“beyond-use-date” or BUD), and 4) ask the compounding pharmacist for evidence that the compounded drug is safe and effective.

Also recognize that most state boards of pharmacy require that an out-of-state pharmacy register with their state prior to filling prescriptions to be mailed into their state. Veterinarians can inquire with their state board of pharmacy to ascertain the status of a pharmacy’s license and to gain valuable information including the pharmacy permit number.

If you observe unanticipated drug precipitation, visible flocculant material, color change or separation of liquid phases with a compounded preparation, these changes may indicate improper storage, transport, or an unexpected chemical/physical drug interaction. If you have questions about the efficacy or safety of the preparation, consult with the compounding pharmacist.

Q: What is the expiration date for compounded drugs?A: Veterinarians should inquire as to how the beyond-use date was established. Beyond-use dates and expiration dates are not the same. Expiration dates for the chemical and physical stability of manufactured products are determined from results of rigorous analytical and performance testing, and they are specific for a particular formulation in its container and at stated exposure conditions. According to the United States Pharmacopeial Convention (USP) (e.g. General Chapters <795> and <797>), the compounding pharmacist is responsible for setting the beyond-use date within the conservative default parameters established by USP.

Q: What is the difference between “potency” and “stability” testing in determining the beyond-use date (BUD) of a compound? A: Potency testing measures the concentration of drug in a compound at a given point in time. Stability testing measures the amount of active drug remaining AND measures the amount of degraded drug byproducts present at a given time. Stability testing allows determination of a true beyond-use date (BUD).

Q: How do I know if the compound is bioavailable (e.g., being absorbed and reaching desired blood levels)?A: You don’t. Veterinarians should seek results from scientifically designed studies demonstrating the efficacy and safety of a particular preparation, including drug delivery systems in the target species. These study results showing suitable stability, relative efficacy, and safety in the target species can be considered in the benefit-risk analysis a veterinarian performs when deciding whether to use the particular preparation in the patient. For example, some drugs are specially formulated by their manufacturers with various chemical complexes that allow them to be absorbed from animal gastrointestinal tracts. The bulk chemical for these drugs might not be absorbed appreciably from the animal’s gastrointestinal tract and blood levels cannot be assured from compounds of these and many other drugs. Therefore, objective therapeutic monitoring is critical when using compounds in your patients.

Q: What's my liability if there's a problem with a compounded medication? A: If you have a potential claim situation, you should always contact your liability carrier.

Insurance carriers are unable to provide an unequivocal statement on the potential liability and related insurance coverage associated with compounding because the subject is a complex mix of state and federal regulations; with many situational variables, and a history of varying and unpredictable degrees of enforcement.

Q: How many refills can be ordered on a compounded prescription?A: We are unaware of any differences between refilling compounded preparation prescriptions versus other refills. However, to be certain you are following the applicable rules for your state, check your state’s veterinary medical and pharmacy rules. Due to the short beyond-use dates (BUDs) on some compounds, more frequent refills may be indicated.

Q: Can controlled substances be compounded? (And if so, how does the process differ from compounding non-controlled substances?) A: Yes, but remember you will need to follow the Food and Drug Administration’s (FDA) rules, the state’s rules, and the Drug Enforcement Administration’s (DEA) rules. When you prescribe a compounded controlled substance, be sure that the compounding pharmacy is dispensing the product directly to your client/patient. If you do this, you’re maintaining what federal authorities refer to as a “closed distribution system.”

However, if you allow the compounding pharmacy to deliver the controlled substance product to your clinic for your client to pick up, now you’ll need to enter that delivery into your controlled substance records because you’ve just received controlled substance inventory which must, by law, be tracked through recordkeeping. This may be necessary if the drug needs to be compounded for use within your clinic (for example, if the drug is needed for your patient who is being hospitalized), but recognize that receipt of the drug from the pharmacy is a registrant-to-registrant transfer of controlled substances for which DEA has very specific rules. In this case, your records need to show the flow through the clinic at a high level of detail, like any other shipment of controlled substances you receive.

Q: Is it okay to prescribe a compounded medication that is the same as an available brand-name or generic medication because it's cheaper in the compounded form? A: It is not appropriate to select a compounded drug for a patient solely for economic reasons based on FDA’s Extralabel Drug Use Rules.

Q: Can a client use a compounded medication for another pet/animal they own? A: Check your state's pharmacy rules to be sure but, in general, if you are treating animals as a group, herd, or flock and you have an established Veterinarian-Client-Patient Relationship (VCPR), it would be acceptable to provide one prescription or dispensed product with directions for treating the group. However, you must have determined that the compounded drug is necessary for those animals, you are following FDA’s Extralabel Drug Use Rules, (or see our brochure for an algorithm) and the patients are to be treated as a group (e.g. a litter of puppies being treated for coccidia). If the animals are to be treated as individuals, separate prescriptions are advised in order to ensure client compliance and effective treatment. Be sure you keep accurate records and label the drug accordingly.

Regardless of the number of animals for which the prescription is filled, the AVMA recommends that the following information be clearly included on the label. (For more information, see the AVMA's Guidelines for Veterinary Prescription Drugs and be sure to check your state's pharmacy and veterinary practice rules, as well.)

Name, address, and telephone number of veterinarians

Name of clients

Identification of animal(s) treated, species and numbers of animals treated, when possible

Date of treatment, prescribing, or dispensing of drug

Name, active ingredient, and quantity of the drug (or drug preparation) to be prescribed or dispensed

Drug strength (if more than one strength available)

Dosage and duration

Route of administration

Number of refills

Cautionary statements, as needed

Expiration date or beyond-use date (BUD) if applicable

Slaughter withdrawal and/or milk withholding times, if applicable

The actual container must bear the veterinarian's name, address, name of the drug (active ingredient), identification of the animal(s) to be treated, adequate directions for proper use, and cautions/precautions including milk and meat withdrawal times. This information may be on the label applied by the manufacturer, or on a label attached to the product by the veterinarian or compounding pharmacist.

Q: How do I register a possible adverse event or complaint about a compounded medication or a compounding pharmacy?A: Veterinarians should report suspected adverse events or product failures involving compounded preparations to the compounding pharmacist, the state board of pharmacy and the FDA Center for Veterinary Medicine. Instructions for reporting adverse events to FDA can be found on the FDA website.

Pharmacists should instruct pet owners to contact both the prescribing veterinarian and pharmacist immediately if a compounded preparation has caused an adverse event.

If an unlawful pharmacy practice is suspected, the AVMA also has a complaint form that members can fill out and send to their respective state board of pharmacy, the state board where the pharmacy is located, and the FDA. Carbon copies can be sent to AVMA for archiving purposes.

Q: What is a bulk drug?A: Simply put, a bulk drug is a raw drug active pharmaceutical ingredient (API) or pure chemical used to create a finished dosage form. In other words, it’s the chemical ingredient used to produce the drug, whereas the FDA-approved version is the actual finished form containing the ingredient.

Q: Is it legal to compound from bulk chemicals?A: The FDA contends that compounding from bulk pharmaceutical ingredients for animals has been illegal for many years and continues to be illegal.

That said, the FDA recognizes the medical need for compounding from bulk ingredients within certain areas of veterinary practice and under very specific circumstances. Specifically, in its Compliance Policy Guide, the FDA lists a series of poison antidotes and indicates that it would not ordinarily object to use of these antidotes (which are only available as bulk drugs).

The following are situations where the AVMA believes a veterinarian may find that s/he needs a compounded preparation from a bulk ingredient for use in a non-food animal:

The FDA-approved drug is not commercially available; or

The needed compounded preparation cannot be made from the FDA-approved drug.